Non-myeloablative stem cell transplantation (Nst) For the treatment of malignant and non-malignant diseases

Abstract

Abstract We have developed non-myeloablative stem cell transplantation (NST), using Fludarabine-based regimen (30 mg/m 2 /day × 6) in conjunction with either oral Busulfan (4 mg/Kg/day × 2) or higher doses in children due to rapid pharmakotinetics; Cytoxan (5 mg/Kg/day × 2) in Fanconi's anemia or 60 mg/Kg × 2 in severe aplastic anemia with ATG (fresenius) (5 to 10 mg/Kg/day × 4) or using single low dose total body irradiation (TBI) 200 cGY. Included were patients with hematologic malignancies (acute & chronic leukemia, lymphoma, MDS) and patients with non-malignant hematologic disease (aplastic anemia, Fanconi's anemia, Gauchers', osteopetrosis, chronic granulomatosis disease, Thalassemia major and Diamond Blackfand Syndrome). NST was also tried in a cohort of 16 patients with matched unrelated donor, as well as in 11 patients who failed prior myeloablative stem cell transplantation. Engraftment was observed in all patients with a matched donor available with minimal or no aplasia. Procedure-related toxicity and mortality was low, but GVHD was still the single major problem. The clinical outcome of patients belonging to all NST subgroups will be updated. The data suggest that following induction of host vs graft tolerance, donor immunocompetent cells can displace and replace host with donor immunohematopoietic cells. NST may become the treatment of choice for patients in need of allogeneic stem cell transplantation for malignant and non-malignant diseases.